Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis.

Published online

Journal Article

Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.The molecular mechanisms mediating the impact of environmental factors in atherosclerosis are unclear. Here, the authors examine CD14+ blood monocyte's transcriptome and epigenome signatures to find differential methylation and expression of ARID5B to be associated with human atherosclerosis.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Reynolds, LM; Ding, J; Hou, L; Lohman, K; Young, T; Cui, W; Huang, Z; Grenier, C; Wan, M; Stunnenberg, HG; Siscovick, D; Hou, L; Psaty, BM; Rich, SS; Rotter, JI; Kaufman, JD; Burke, GL; Murphy, S; Jacobs, DR; Post, W; Hoeschele, I; Bell, DA; Herrington, D; Parks, JS; Tracy, RP; McCall, CE; Stein, JH

Published Date

  • August 30, 2017

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 393 -

PubMed ID

  • 28855511

Pubmed Central ID

  • 28855511

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-017-00517-4

Language

  • eng

Conference Location

  • England